| Suppression
of Human Rheumatoid Synovial Fibroblast MMP-2 Expression and Marix
Invasion by Nutrient Synergy
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Matthias Rath Research, Cancer Research Division, Santa Clara,
CA 95050
Presented at: 9th World Congress of the Osteoarthritis
Research Society International, Chicago, Illinois, December 2-5,
2004.
Published in: Osteoarthritis and Cartilage,
Abstract #193.
Abstract
Objective:
In patients with rheumatoid arthritis and other inflammatory diseases,
MMPs are expressed in synovial membranes and have been implicated
in synovial tissue invasion into adjacent cartilage and bone.
We investigated the effect of a unique nutrient mixture (NS) containing
ascorbic acid, lysine, arginine, and epigallocatechin gallate
on human synovial fibroblast growth, MMP expression, and invasive
potential.
Materials and Methods:
Human synovial fibroblasts (CHTN) were grown in DME medium supplemented
with 10% FBS, penicillin (100 U/ml) and streptomycin (100 mg/ml)
in 24-well tissue culture plates. At near confluence, the cells
were treated with NS dissolved in media and tested at 0, 10, 100,
500, and 1000 ?g/ml in triplicate at each dose. Cell proliferation
was evaluated by MTT assay, MMP expression by gelatinase zymography,
and invasion through Matrigel.
Results:
NS demonstrated dose-dependent inhibition of synovial fibroblast
growth with maximum inhibition of 49% at 1000 µg/ml (p<
0.0001). NS was found to inhibit synovial fibroblast expression
of MMP-2 in a dose-dependent manner, with complete inhibition
at 500 µg/ml. The synergistically acting nutrient mixture
significantly reduced the invasion of human synovial fibroblasts
through Matrigel in a dose-dependent fashion, with 89% inhibition
at 100 µg/ml and 100% at 500 µg/ml NS (p=0.01). H&E
staining demonstrated no major changes, even at the highest concentration
of NS.
Conclusion:
Our results suggest that this nutrient mixture has excellent potential
as an anti-inflammatory agent to suppress synovial cell MMP-2
activity and tissue invasion.
Comments
In patients with rheumatoid arthritis and other inflammatory
diseases, MMPs are expressed in synovial membranes and have
been implicated in synovial tissue invasion into adjacent
cartilage and bone. Standard anti- arthritic drugs, used for
prolonged periods, have been associated with serious side
effects. We studied the in vitro effect of a mixture of nutrients
containing ascorbic acid, lysine, arginine and epigallocatechin
gallate on human synovial fibroblast growth, MMP expression,
and invasive potential. Our results demonstrated complete
inhibition of MMP-2 expression and invasive potential of synovial
fibroblasts at 500 µg/ml, suggesting this nutrient mixture
has excellent potential as a safe anti-inflammatory agent. |
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